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White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/126954/
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Article:
Abignano, G, Fadl, N, Merashli, M et al. (4 more authors) (2018) Apremilast for the treatment of active psoriatic arthritis: a single-centre real-life experience. Rheumatology, 57 (3). pp. 578-580. ISSN 1462-0324
https://doi.org/10.1093/rheumatology/kex454
© The Author(s) 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is a pre-copyedited, author-produced PDF of an article published in Rheumatology following peer review. The version of record: Giuseppina Abignano, Nafisa Fadl, Mira Merashli, Claire Wenham, Jane Freeston, Dennis McGonagle, Helena Marzo-Ortega; Apremilast for the treatment of active psoriatic arthritis: a
single-centre real-life experience, Rheumatology, Volume 57, Issue 3, 1 March 2018, Pages 578–580, is available online at: https://doi.org/10.1093/rheumatology/kex454
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Apremilast for the treatment of active psoriatic arthritis: a single centre real-life
experience
Giuseppina Abignano1-3, Nafisa Fadl 1,2, Mira Merashli1,2, Claire Wenham1,2, Jane
Freeston1,2, Dennis McGonagle1,2, Helena Marzo-Ortega1,2
1. NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust,
Leeds, UK
2. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK
3. Rheumatology Institute of Lucania (IReL), Rheumatology Department of Lucania, San
Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera,
Potenza, Italy
Correspondence to: Helena Marzo-Ortega, LIRMM, Second floor, Chapel Allerton
Hospital, Chapeltown Road, Leeds LS7 4SA, United Kingdom. E-mail:
medhmo@leeds.ac.uk
Key message: Real life experience of apremilast in PsA suggests enhanced efficacy in
Sir, Apremilast (Otezla; Celgene, Summit, NHJ, USA) is a small-molecule
phosphodiesterase-4 inhibitor which offers a novel oral therapeutic option for
patients with psoriasis (Pso) and psoriatic arthritis (PsA). Recent randomized
controlled trials (RCTs) show that Apremilast is effective in both Pso and PsA (1-6)
however there are still a paucity of real-life data in unselected patients.
We performed, at our tertiary centre, a retrospective analysis of the effectiveness and
tolerability of Apremilast at a standard dose of 30 mg BID in subjects with PsA treated in
a dedicated out-patient clinic following a Zero cost scheme prior to NICE approval in the
UK.
All subjects fulfilled Classification Criteria for PsA (CASPAR) (7) and had active disease
according to the treating clinician. In addition, all subjects had previously been exposed to
adequate trials of DMARDs. Ethical approval was not required as this report was an audit
of standard practice and service evaluation.
As part of our local clinic algorithms, subjects were assessed at baseline and every 6 (±3)
months. Clinical assessments at each visit included tender (0-78) and swollen (0-76) joint
count and C-reactive protein (CRP) levels. When patient and physician global assessment
on a 5-point Likert scale were available on clinical notes review, PsA response criteria
(PsARC) were also calculated (8).
Subjects were classified as responders and non-responders based on the overall physician
judgement of clinical status (yes/no), specifically: the absence of peripheral arthritis,
enthesitis and dactylitis on clinical examination; or improvement of clinical signs at
PsARC. Response was defined based on the last available follow-up assessment as
compared with the baseline evaluation.
Binomial variables were expressed as number and percentages, continuous variables as
median (range) or mean±SD as appropriate. Comparison between baseline and follow-up
measurements was performed using Wilcoxon matched-pairs signed rank test. Significant
differences between responders and non-responders were defined as those at a level of
p<0.05, by unpaired t-test or Fisher’s/chi-square test. Statistical analysis was carried out
using GraphPad Prism software V.7.0.
A total of 71 patients (n=33 [46.5%] male) with a mean follow-up of 172.6±105.5 days
were identified and included in this report. Clinical characteristics are summarized in Table
1. Of the 71 patients started on Apremilast, 51 had at least a 6 (±3) months follow-up
assessment. Based on overall clinician judgement, 31 out of 51 (60.8%) patients were
classified as responders and 20 (39.2%) as non-responders. In patients in which joint count
was recorded at the baseline and at the follow-up assessment (n=22), there was a
statistically significant improvement of tender (p=0.004) and swollen (p=0.003) joint count.
In patients with abnormal CRP levels at baseline, measurements slightly decreased at
follow-up (p=0.04). Of note, responders had a shorter disease duration compared to
non-responders (5.23±4.46 vs 9.15±6.8 years, p=0.016), and had a lower exposure to previous
biological DMARDS (bDMARDS) (p=0.0055) and conventional or synthetic DMARDS
(cDMARDS), although this latter difference did not reach statistical significance (p>0.05).
No other significant differences were found between the two groups.
developed one or more side effects (Table 1). The most common side effects were
gastro-intestinal (GI) symptoms (19/71) including: nausea (9/71), vomiting (3/71), diarrhea (13/71)
and abdominal pain with loss of appetite (1/71). Two patients experienced depression
(2.8%), of which one had associated suicidal ideation and concomitant headache and GI
symptoms which required drug withdrawal within the eighth week.
To our knowledge, this is the first real-life report of the use of Apremilast in unselected
PsA patients. Previously published RCTs showed that Apremilast is effective in patients
with PsA and Pso with an acceptable safety profile. In patients with PsA treated with
apremilast 30 BID, ACR20 response ranged between 32.1% and 41% at week 16, in three
different phase III RCTs (4-6). Despite using different response criteria, our data from an
unselected tertiary centre population confirm these results. A main limitation of our report
are the low numbers treated and the amount of missing data which reflects a real population
observation, and is in part due to the use of paper based assessments in our hospital.
An important observation however and despite the low numbers, is that clinical response
appeared to be enhanced in the subset of patients with shorter disease duration suggesting
that apremilast may be better placed earlier on in the treatment algorithm for PsA although
this observation would need to be confirmed with larger numbers.
In conclusion, our data provide real life evidence of the short-term efficacy of apremilast
in the treatment of active PsA and suggest that this may be enhanced in the earlier disease
stages. Apremilast represents a valuable, additional, oral, synthetic molecule for the
treatment of PsA. Larger observational cohort studies with health economic evaluation will
Acknowledgements
GA was supported by a grant from the Fondazione Italiana per la Ricerca sull’Artrite
(FIRA ONLUS). The research was supported by the National Institute for Health Research
(NIHR) Leeds Biomedical Research Centre. The views expressed are those of the authors
and not necessarily those of the NHS, the NIHR or the Department of Health.
Funding: No specific funding was received from any bodies in the public, commercial or
not-for-profit sectors to carry out the work described in this manuscript.
Disclosure statement: H.M.-O. has received grants and/or honoraria from Abbvie,
Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. G.A. has received honoraria from
Celgene, UCB, Pfizer, Italfamaco, Actelion and MSD. D.G.M. has undertaken research
and/or educational programme activity with Pfizer, MSD, AbbVie, BMS, UCB, Novartis,
Celgene and Johnson & Johnson. All other authors have declared no conflicts of interest.
REFERENCES
1. Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4
(PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a
phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the
Effects of Apremilast in Psoriasis [ESTEEM 1]). J Am Acad Dermatol
2015;73:37-49.
over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2). Br J
Dermatol 2015;173:1387-99.
3. Schett G, Wollenhaupt J, Papp K, et al. Oral apremilast in the treatment of active
psoriatic arthritis: results of a multicenter, randomized, double-blind,
placebo-controlled study. Arthritis Rheum 2012;64:3156–67.
4. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in
a phase 3 randomised, placebo-controlled trial with apremilast, an oral
phosphodiesterase 4 inhibitor. Ann Rheum Dis 2014;73:1020–6.
5. Cutolo M, Myerson GE, Fleischmann RM, et al. A phase III, randomized, con-
trolled trial of apremilast in patients with psoriatic arthritis: results of the PALACE
2 trial. J Rheumatol 2016;43:1724–34.
6. Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4
inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase
III, randomised, controlled trial (PALACE 3). Ann Rheum Dis 2016;75:1065–73.
7. Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic
arthritis: development of new criteria from a large international study. Arthritis
Rheum 2006;54:2665–73.
8. Mease PJ, Goffe BS, Metz J, et al. Etanercept in the treatment of psoriatic
Table 1. Baseline clinical characteristics of 71 PsA patients treated with Apremilast
Male, n (%) 33 (46.5)
Age, years, mean (SD) 51, 13.2
DD PsA, years, mean (SD) 7.7, 6.4
Peripheral involvement (all poly-articular), n (%) 71 (100)
Axial involvement, n (%) 22 (31)
Psoriasis, n (%) 59 (83.1)
Nail involvement, n (%) 20 (44.4)
Entheseal/Dactylitis involvement, n (%) 38 (60.3)
CRP baseline, mg/L, median (range) 7.1 (5-115)
Tender Joints count, median (range) 7 (0-40)
Swollen Joints count, median (range) 3 (0-16)
Patient’s disease activity, 1-5, median (range) 4 (1-5)
Physician’s disease activity, 1-5, median (range) 3 (1-5) Current cDMARDS
MTX
SZ
HCQ
Leflunomide
Combination (MTX + SZ, MTX +HCQ)
Previous bDMARDS, n (%) 40 (56.3)
Contraindication to bDMARDS, n (%) 10 (14.1)
Apremilast discontinuation, n (%)
Ineffective
Side effects:
GI symptoms
General malaise
Headache
Depression, suicidal ideation
28 (39.4)
11 (15.5)
27 (38)
19
2
8
2, 1
Time to discontinuation, days
mean (SD)
median (range)
129.7 (77.7)
132 (21-313)
Time of follow-up, days
mean (SD)
median (range)
172.6 (105.5)
153 (21-519)
